Ilene Kay Gipson, Ph.D.

Harvard Medical School

Schepens Eye Research Institute of Massachusetts Eye and Ear

Research Summary

Center/Research Area Affiliations

Biography

Dr. Gipson began her career in vision research at the University Of Oregon Health Sciences Center, where she became an Assistant Professor of Ophthalmology. In 1979, she was recruited to the Schepens Eye Research Institute of Mass. Eye and Ear (then Eye Research Institute of the Retina Foundation). She rose through the ranks from Assistant to Senior Scientist at the Institute, and in 1997, became Professor of Ophthalmology at Harvard Medical School and also the Ocular Surface Scholar at the Institute.

Previously, Dr. Gipson’s research focused on epithelial wound healing and anchorage, using the accessible corneal epithelium as a model system. More recently, she has focused on the function of mucins on the ocular surface epithelia and their alteration in disease and infection. She has determined regulators of goblet cell differentiation at the ocular surface, and the role of their secreted mucins, in ocular surface health. Most recently, she determined the important barrier function of membrane anchored mucins present in the ocular surface glycocalyx, documenting their role in preventing infections.

Dr. Gipson has received numerous awards, including the MERIT Award from the National Eye Institute and the Research to Prevent Blindness Senior Scientific Investigator Award. In May 2007, Dr. Gipson received The Friedenwald Award—one of two achievement awards given annually at the Association for Research in Vision and Ophthalmology meeting—in honor of her outstanding research.

Her Story

Dr. Gipson studies the ocular surface. This structure at the front of the eye enables and protects vision. Therefore, diseases that affect it can be devastating and are among the leading causes of blindness and vision impairment worldwide.

What is the ocular surface?

The ocular surface is the layer of cells at the front of the eye—those cells that come in contact with the outside world. These cells cover the cornea (the clear covering of the eye) and the conjunctiva (the white of the eye and the inner eyelids) and form the lacrimal and Meibomian glands. Each layer of cells that form these surfaces is called an epithelium (they are shown in pink in the diagram). Each region of the ocular surface epithelium produces components that help form the tear film, which keeps the surface of the eye moist and protected from pathogen invasion.

How does the ocular surface enable vision?

The major way in which the ocular surface enables vision is that it bends (refracts) light so that the light can focus on the retina. The cornea is where most of the eye’s refraction occurs. To bend light, the ocular surface is both curved and exceptionally smooth. Maintaining this smooth, wet surface on the cornea requires the secretion the tear film. This film has an outer lipid layer, secreted by the Meibomian glands, that prevents the tears from drying out. The film also contains watery tears that are produced by the lacrimal glands. Importantly, maintaining the smooth surface also requires keeping the tears and lipids in place on the epithelial surface.

The surface of the epithelia of the cornea and conjunctiva produces at its tear-film surface, a class of molecules that help hold the watery layer onto the surface of the eye. These molecules are very hydrophilic, or “water loving.” They act as sponges, keeping the tears on the ocular surface. They also provide a barrier that prevents entry of pathogens into the epithelium. This class of molecules is called mucins. Mucins are made by all of the wet epithelia of the body, including the epithelia that are on the surface of the gastrointestinal, respiratory, and reproductive tracts (but not the skin). All of us who have had a bad cold know about the mucus that results from infection. The major component of mucus is mucins.

Researchers in Dr. Gipson’s laboratory are experts in mucin biology, primarily as these molecules relate to the ocular surface. However, the laboratory has also made major contributions regarding mucins and reproductive-tract function.

What diseases affect the ocular surface and interfere with vision?

Many diseases affect the ocular surface. Some of the major ones include dry eye diseases, infections, immune diseases that affect the ocular surface, and vitamin A deficiency (a problem in some developing countries).

How are mucins involved in these diseases?

The Gipson laboratory has demonstrated an alteration in epithelial surface mucins in several types of dry eye, and has data showing that loss of surface mucins allows penetrance into the corneal epithelium of the dyes that are used to diagnose dry eye disease. This indicates that mucins are lost from the epithelial surface in dry eye.

Recent data from the Gipson laboratory show that these surface mucins provide a barrier, to prevent bacteria from sticking to the ocular surface cells. Because infections of the surface of the eye often occur if the surface of the eye is dry or injured, this implies that the mucin barrier has been removed or altered. In some of the immune-system diseases that affect the ocular surface, drying occurs with loss of mucins and, in animal models of vitamin A deficiency, mucin genes are less active, causing the loss of mucins on the ocular surface.

What have we learned about preventing or treating these diseases?

We developed human ocular-surface epithelial cell-culture systems so that we can find factors that up regulate mucin gene expression, thereby enhancing protection and tear retention. We have found several agents that affect mucin production and removal from the ocular surface. We hope that, by understanding these processes, we will find new therapies for dry eye and for protecting those eyes that are at risk of infection.

Projects

Research Interests

How mucins affect the ocular surface epithelia and influence disease and infection

Mucins and the Ocular Surface

The stratified epithelium over the surface of the eye is the first line of defense for the visual system, protecting it from invasion by pathogens, from desiccation, and from injury and abrasion. Dr. Gipson is interested in the structure and function of the large protective glycoproteins, known as mucins, that the epithelium synthesizes and secretes onto the surface of the eye.

All wet-surfaced epithelia of the body express multiple mucin genes of two types at their apical surface. One type—secreted mucins—is made by goblet cells and/or glandular cells. This type of mucin is moved over the surface of epithelia to remove debris and maintain fluid at the epithelial surface. The second type—membrane-associated mucins—have short cytoplasmic tails that are present in apical membranes of the epithelia. The specific functions of members of this class of mucins are not known.

The ocular surface is an excellent model system to study mucins, as both types are expressed. Our laboratory studied the function of individual mucins (MUCs 1, 4 and 16 of the membrane type and MUC5AC of the secreted type), using molecular techniques and functional assays we have developed. We demonstrated alteration of mucins in drying eye diseases and are studying the nature of these alterations for potential therapeutic intervention.

Research Funding

Dr. Gipson was funded by R01 EY03306 for 40 years dating from 1976. In 2016 she closed her laboratory and is currently active in writing and reviewing .

Publications

H-index

62 (Google Scholar, as of September 2017)

Selected Publications

Dr. Gipson has published more than 150 peer-reviewed articles. Below is a list of recent publications. View her publications on PubMed.